We propose that tumors of skin can be induced in a manner similar to the classical "two-stage theory of carcinogenesis". The cocarcinogen is postulated to be a specific growth factor, found in high quantities in the male mouse submaxillary gland, which has epithelial tissue as its target. Epithelial Growth Factor (EGF) promotes precocious and hypertrophic development of epithelial tissue early in development. We propose that high levels of EGF provoke hyperproliferative responses in the epithelial cells, rendering them sensitive to transformation by a topical carcinogen. We further propose that, in analogy with recently isolated ovarian, liver, and mammary tumors and cell lines dependent for growth on steroid hormones, insulin and prolactin respectively, EGF-dependent skin tumors will be induced. To test this hypothesis the correlation between tumor succeptibility and EWF serum and salivary levels will be examined. Mice of appropriate strains will be exposed to chemical carcinogens and high levels of purified EGF. Induced tumors will be transplanted to inbred recipients, and tested for EGF dependence by concomitant administration of anti-EGF antisera. Tumors will be adapted to cell culture by alternate culture and passage. EGF-dependent clonal cell lines will be isolated from EGF-dependent tumors by appropriate selection techniques.